The overall objectives of the research proposed in this application are to examine the effects of alcohol on the hypothalamic-pituitary-gonadal axis in the male rat. It has been well established that chronic alcoholics have many symptoms of hypogonadism (such as low serum testosterone levels, testicular atrophy and gynecomastia), loss of libido, impaired sexual performance and somewhat questionable fertility. The purpose of the studies described in this application is to examine the ways in which alcohol specifically interferes with the function of the hypothalamic-pituitary-gonadal axis. To this end the following general sets of in vivo and in vitro studies will be conducted: (1) the effects of alcohol on the hypothalamic-pituitary axis will be rigorously examined; (2) the effects of alcohol on pituitary-gonadal function will be evaluated; (3) the effects of alcohol on the gonadal-target organ axis will be investigated; (4) the effects of alcohol on the metabolism of testosterone will also be examined; and (5) to examine the consequences of acute or long-term perturbations in endocrine function with respect to the pharmacological actions of alcohol, particularly the development of tolerance and physical dependence. These experiments have been designed to exhaustively examine the effects of alcohol at each major control point in the hypothalamic-pituitary-gonadal axis. Their purpose is to ultimately lead to a complete understanding of the mechanisms underlying the adverse effects of alcohol on human sexual function and reproductive behavior and to elucidate the role of hormones in the actions of alcohol.